Serotonin-2A-receptor and -transporter polymorphisms: lack of association in patients with major depression
Serotonin-2A-receptor and -transporter polymorphisms: lack of association in patients with major depression
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DOI：
10.1016/s0304-3940(01)01704-9
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发表时间：
2001-05
影响因子：
2.5
通讯作者：
C. Minov;T. Baghai;C. Schüle;P. Zwanzger;M. Schwarz;P. Zill;R. Rupprecht;B. Bondy
中科院分区：
文献类型：
--
作者：
C. Minov;T. Baghai;C. Schüle;P. Zwanzger;M. Schwarz;P. Zill;R. Rupprecht;B. Bondy
5 -羟色胺能神经传递系统的紊乱与情绪障碍的病因有关。由于遗传因素的重要性已经确立，编码血清素能途径蛋白质的基因是揭示潜在遗传贡献的重要候选者。我们在173名重度抑郁症患者和121名健康对照中检测了血清素- 2a受体基因（5-HT2A、T102C和His452Tyr）的两种多态性以及血清素转运体启动子区域（5-HTTLPR）的插入/缺失多态性。无论是基因型的分布还是等位基因的频率，在患者和对照组之间的三种被调查的多态性都没有发现统计学上的显著差异。而在5-HTTLPR多态性方面，S/S（短等位基因）纯合子频率（23.1%）高于对照组（14.0%），但未达到显著性。此外，我们观察到具有一个或两个T102C多态性c等位基因的患者的治疗反应不同，在抗抑郁治疗4周后，HAMD-17的下降幅度显著更高（方差分析：d.f =1， F= 5288， P=0.023）。总之，我们的研究结果表明，所研究的5-HT2A和5-HTTLPR多态性不是重度抑郁症病因的主要易感因素。然而，亚型至少可以根据不同的治疗反应来确定。
Disturbances in serotonergic neurotransmission system have been implicated in the etiology of mood disorders. As the importance of genetic factors is well established, genes encoding for proteins of the serotonergic pathway are important candidates to unravel the underlying genetic contribution. We examined two polymorphisms in the serotonin-2A-receptor gene (5-HT2A; T102C and His452Tyr) and the insertion/deletion polymorphism in the promoter region of the serotonin transporter (5-HTTLPR) in a sample of 173 patients with major depression and 121 healthy controls. No statistical significant differences between patients and controls were found for any of the three investigated polymorphisms, neither in the distribution of the genotypes nor in allele frequencies. However, concerning the 5-HTTLPR polymorphism, the frequency of S/S (short allele) homozygotes was higher (23.1%) than in the control group (14.0%), but this failed to reach significance. Moreover we observed a different treatment response in patients with one or two C-alleles of the T102C polymorphism, with a significantly higher decrease in HAMD-17 (ANOVA: d.f.=1, F=5,288, P=0.023) after 4 weeks of antidepressant treatment. Overall our results suggest that the investigated 5-HT2A and 5-HTTLPR polymorphisms are not major susceptibility factors in the etiology of major depression. However, subtypes might be identified at least on a basis of differential treatment response.